This invention relates to a new and useful process for preparing a known 4,4-diphenylbutanoic acid derivative. More particularly, it is concerned with a novel three-step process for preparing 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid, which serves as a key intermediate in the production of the antidepressant agent known as cis-(1S)(4S)-N-methyl-4-(3,4-dichlorophenyl)1,2,3,4-tetrahydro-1-naphthale neamine (sertraline) via 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone. The invention also includes within its scope such novel compounds as 4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid and 5-(3,4-dichlorophenyl)-dihydro-2(3H)-furanone, which are used as intermediates in the aforesaid three-step novel process. The invention additionally includes a novel process for converting both 4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid and 5-(3,4-dichlorophenyl)-dihydro-2(3H)-furanone directly to the aforesaid 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)naphthalenone.
In accordance with the prior art, there is described in U.S. Pat. No. 4,536,518 to W. M. Welch, Jr. et al., as well as in the paper of W. M. Welch, Jr. et al. appearing in the Journal of Medicinal Chemistry, Vol. 27, No. 11, p. 1508 (1984), a method for preparing certain 4-(substituted phenyl)-4-(optionally-substituted phenyl)butanoic acids wherein the optional substituent is always other than alkoxy. These particular 4,4-diphenylbutanoic acid derivatives are shown to be useful as intermediates that lead to various antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthaleneamine, including cis-(1S)(4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene amine (sertraline) which is an especially preferred embodiment in this series. The prior art method disclosed in the aforesaid publications of W. M. Welch, Jr. et. al. involves synthesizing the desired 4,4-diphenylbutanoic acid intermediates in a plurality of steps starting from the corresponding benzophenone compound. For instance, the appropriately substituted benzophenone starting material is first subjected to a base-catalyzed Stobbe condensation with diethyl succinate, followed by hydrolysis and decarboxylation with 48% aqueous hydrobromic acid to yield the corresponding 4,4-diphenylbut-3-enoic acid, which is thereafter reduced by catalytic hydrogenation or by the use of hydriodic acid and red phosphorus to finally yield the desired 4,4-diphenylbutanoic acid intermediate.